Strong One-Dimensional Characteristics of Hole-Carriers in ReS2 and ReSe2.

Each plane of layered ReS2 and ReSe2 materials has 1D chain structure, from which intriguing properties such as 1D character of the exciton states and linearly polarized photoluminescence originate. However, systematic studies on the 1D character of charge carriers have not been done yet. Here, we report on systematic and comparative studies on the energy-momentum dispersion relationships of layered transition metal dichalcogenides ReS2 and ReSe2 by angle resolved photoemission. We found that the valence band maximum or the minimum energy for holes is located at the high symmetric Z-point for both materials. However, the out-of-plane ([Formula: see text]) dispersion for ReSe2 (20 meV) is found to be much smaller than that of ReS2 (150 meV). We observe that the effective mass of the hole carriers along the direction perpendicular to the chain is about 4 times larger than that along the chain direction for both ReS2 and ReSe2. Remarkably, the experimentally measured hole effective mass is about twice heavier than that from first principles calculation for ReS2 although the in-plane anisotropy values from the experiment and calculations are comparable. These observation indicate that bulk ReS2 and ReSe2 are unique semiconducting transition metal dichalcogenides having strong one-dimensional characters.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

NAD(P)H-quinone oxidoreductase 1 silencing aggravates hormone-induced prostatic hyperplasia in mice.

NAD(P)H-quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone-induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild-type (WT) and NOQ1 knockout C57BL/6 mice (NQO1-/- ) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone-treated NQO1-/- showed about 140% higher prostate weight than the testosterone-treated WT, with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO1-/- . In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1-/- prostate confirmed aggravated prostatic hyperplasia in NQO1-/- . Moreover, the expression of heat shock protein (HSP) 90-α was markedly increased in the NQO1-/- , and this was supported by increased testosterone-induced nuclear androgen receptor expression in NQO1-silenced LNCaP cells. Testosterone-induced prostate-specific antigen expression was not reversed in NOQ1-silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α-reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90-α expression.

Possible electric field induced indirect to direct band gap transition in MoSe2.

Direct band-gap semiconductors play the central role in optoelectronics. In this regard, monolayer (ML) MX2 (M = Mo, W; X = S, Se) has drawn increasing attention due to its novel optoelectronic properties stemming from the direct band-gap and valley degeneracy. Unfortunately, the more practically usable bulk and multilayer MX2 have indirect-gaps. It is thus highly desired to turn bulk and multilayer MX2 into direct band-gap semiconductors by controlling external parameters. Here, we report angle-resolved photoemission spectroscopy (ARPES) results from Rb dosed MoSe2 that suggest possibility for electric field induced indirect to direct band-gap transition in bulk MoSe2. The Rb concentration dependent data show detailed evolution of the band-gap, approaching a direct band-gap state. As ionized Rb layer on the surface provides a strong electric field perpendicular to the surface within a few surface layers of MoSe2, our data suggest that direct band-gap in MoSe2 can be achieved if a strong electric field is applied, which is a step towards optoelectronic application of bulk materials.

Hallmarks of the Mott-metal crossover in the hole-doped pseudospin-1/2 Mott insulator Sr2IrO4.

The physics of doped Mott insulators remains controversial after decades of active research, hindered by the interplay among competing orders and fluctuations. It is thus highly desired to distinguish the intrinsic characters of the Mott-metal crossover from those of other origins. Here we investigate the evolution of electronic structure and dynamics of the hole-doped pseudospin-1/2 Mott insulator Sr2IrO4. The effective hole doping is achieved by replacing Ir with Rh atoms, with the chemical potential immediately jumping to or near the top of the lower Hubbard band. The doped iridates exhibit multiple iconic low-energy features previously observed in doped cuprates-pseudogaps, Fermi arcs and marginal-Fermi-liquid-like electronic scattering rates. We suggest these signatures are most likely an integral part of the material's proximity to the Mott state, rather than from many of the most claimed mechanisms, including preformed electron pairing, quantum criticality or density-wave formation.

Classification by causes of dark circles and appropriate evaluation method of dark circles.

BACKGROUND: Dark circles refer to a symptom that present darkness under the eyes. Because of improvement in the quality of life, the dark circles have been recognized as one of major cosmetic concerns. However, it is not easy to classify the dark circles because they have various causes. METHODS: To select suitable instruments and detailed evaluation items, the dark circles were classified according to the causes through visual assessment, Wood's lamp test, and medical history survey for 100 subjects with dark circles. After the classification, were newly recruited for instrument conformity assessment. Through this, suitable instruments for dark circle evaluation were selected. We performed a randomized clinical trial for dark circles, a placebo-controlled double-blind study, using effective parameters of the instruments selected from the preliminary test. RESULTS: Dark circles of vascular type (35%) and mixed type (54%), a combination of pigmented and vascular types, were the most common. Twenty four subjects with the mixed type dark circles applied the test product (Vitamin C 3%, Vitamin A 0.1%, Vitamin E 0.5%) and placebo on randomized split-face for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi L*, quasi a* and dermal thickness) were measured during the study period. Result showed that the L* value of Chromameter(®) , Melanin index (M.I.) of Mexameter(®) and quasi L* value obtained by image analysis improved with statistical significance after applying the test product compared with the placebo product. CONCLUSION: We classified the dark circles according to the causes of the dark circles and verified the reliability of the parameter obtained by the instrument conformity assessment used in this study through the efficacy evaluation. Also based on this study, we were to suggest newly established methods which can be applied to the evaluation of efficacy of functional cosmetics for dark circles.

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-ß signaling.

Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-ß1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-ß receptor III, TßRIII) and in turn induced phosphorylation of TßRI and Smad3 through formation of the TßRIII/TßRII/TßRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.

Analysis of serum protein biomarkers, circulating tumor DNA, and dovitinib activity in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumors.

BACKGROUND: An exploratory translational analysis was conducted as part of a phase II study of dovitinib to assess the relevance of soluble serum proteins and circulating tumor (ct) DNA (ctDNA) as biomarkers in patients with tyrosine kinase inhibitor (TKI)-refractory gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: Predose serum samples were collected from 30 patients on day 1 of cycle 1 and cycle 2. Serum levels of angiogenesis-related proteins were assessed by enzyme-linked immunosorbent assay, and Beads, emulsions, amplification, and magnetics (BEAMing) assays were carried out to detect mutations in serum ctDNA. RESULTS: Dovitinib increased vascular endothelial growth factor (VEGF)165 (1.26-fold, P = 0.006), VEGF-A (1.27-fold, P = 0.004), placental growth factor (6.0-fold, P = 0.002), fibroblast growth factor 23 (1.45-fold, P = 0.02), and interleukin 8 (1.75-fold, P = 0.04) levels, and decreased soluble vascular endothelial growth factor receptor (sVEGFR)-2 levels (0.8-fold, P = 0.001). The changes in sVEGFR-2 were significantly associated with metabolic response determined by positron emission tomography (P = 0.02) and progression-free survival (PFS; P = 0.02). Secondary kinase mutations were identified in the ctDNA of 11 patients (41%), and these patients all had mutations involving KIT exon 17. Patients with secondary KIT mutations had significantly worse overall survival {median, 5.5 months [95% confidence interval (CI) 3.8-7.2 months]} than those with no detectable secondary mutations [9.8 months (95% CI 9.6-10.0 months); hazard ratio = 2.7 (95% CI 1.0-7.3); P = 0.047]. CONCLUSIONS: Changes in sVEGFR-2 levels were associated with dovitinib-mediated antitumor activity. Genotyping of serum ctDNA with BEAMing is useful for the identification of resistant mutations potentially associated with poor prognosis in patients with GISTs.

CD11a, CD11c, and CD18 gene polymorphisms and susceptibility to Behçet's disease in Koreans.

Lesions of Behçet's disease (BD) show vascular infiltrates of immune cells expressing integrins. ß2 integrins (CD11/CD18) play a major role in cell migration to the inflammatory lesion and also induce cytokine production. Thus, genetic polymorphisms of CD11/CD18 may be associated with the pathogenesis of BD. In this study, nine single nucleotide polymorphisms (SNPs) of the CD11a, CD11c, and CD18 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype analysis in 305 BD patients and 266 healthy controls. The frequencies of genotype rs11574944 CC and haplotype rs11574944C-rs2230433G-rs8058823A in CD11a were significantly lower in BD patients. The frequencies of genotype rs2230429 CC, rs2929 GG, and haplotype rs2230429C-rs2929G in CD11c were higher in BD patients. The frequencies of genotype rs235326CC and haplotype rs2070946A-rs235326C-rs760456G-rs684G in CD18 were significantly higher in the BD patients than in the controls. Other SNPs in CD11a, CD11c, and CD18 gene were not significantly different. Therefore, the major genotype and haplotype of CD11a/CD18 may play a role in decreasing the susceptibility of BD, whereas the major genotype and haplotype of CD11c/CD18 may play a role in increasing the susceptibility of BD.

Developmental immunolocalization of the Klotho protein in mouse kidney epithelial cells.

A defect in Klotho gene expression in the mouse results in a syndrome that resembles rapid human aging. In this study, we investigated the detailed distribution and the time of the first appearance of Klotho in developing and adult mouse kidney. Kidneys from 16-(F16), 18-(F18) and 20-day-old (F20) fetuses, 1- (P1), 4- (P4), 7- (P7), 14- (P14), and 21-day-old (P21) pups and adults were processed for immunohistochemistry and immunoblot analyses. In the developing mouse kidney, Klotho immunoreactivity was initially observed in a few cells of the connecting tubules (CNT) of 18-day-old fetus (F) and in the medullary collecting duct (MCD) and distal nephron of the F16 developing kidney. In F20, Klotho immunoreactivity was increased in CNT and additionally observed in the outer portion of MCD and tip of the renal papilla. During the first 3 weeks after birth, Klotho-positive cells gradually disappeared from the MCD due to apoptosis, but remained in the CNT and cortical collecting ducts (CCD). In the adult mouse, the Klotho protein was expressed only in a few cells of the CNT and CCD in cortical area. Also, Klotho immunoreactivity was observed in the aquaporin 2-positive CNT, CCD, and NaCl co-transporter-positive distal convoluted tubule (DCT) cells and type B and nonA-nonB intercalated cells of CNT, DCT, and CCD. Collectively, our data indicate that immunolocalization of Klotho is closely correlated with proliferation in the intercalated cells of CNT and CCD from aging, and may be involved in the regulation of tubular proliferation.

Overexpression of the Brassica rapa transcription factor WRKY12 results in reduced soft rot symptoms caused by Pectobacterium carotovorum in Arabidopsis and Chinese cabbage.

Chinese cabbage (Brassica rapa L. ssp. pekinensis), an important vegetable crop, can succumb to diseases such as bacterial soft rot, resulting in significant loss of crop productivity and quality. Pectobacterium carotovorum ssp. carotovorum (Pcc) causes soft rot disease in various plants, including Chinese cabbage. To overcome crop loss caused by bacterial soft rot, a gene from Chinese cabbage was isolated and characterised in this study. We isolated the BrWRKY12 gene from Chinese cabbage, which is a group II member of the WRKY transcription factor superfamily. The 645-bp coding sequence of BrWRKY12 translates to a protein with a molecular mass of approximately 24.4 kDa, and BrWRKY12 was exclusively localised in the nucleus. Transcripts of BrWRKY12 were induced by Pcc infection in Brassica. Heterologous expression of BrWRKY12 resulted in reduced susceptibility to Pcc but not to Pseudomonas syringae pv. tomato in Arabidopsis. Defence-associated genes, such as AtPDF1.2 and AtPGIP2, were constitutively expressed in transgenic lines overexpressing BrWRKY12. The expression of AtWKRY12, which is the closest orthologue of BrWRKY12, was down-regulated by Pcc in Arabidopsis. However, the Atwrky12-2 mutants did not show any difference in response to Pcc, pointing to a difference in function of WRKY12 in Brassica and Arabidopsis. Furthermore, BrWRKY12 in Chinese cabbage also exhibited enhanced resistance to bacterial soft rot and increased the expression of defence-associated genes. In summary, BrWRKY12 confers enhanced resistance to Pcc through transcriptional activation of defence-related genes.

Comparison of skin elasticity test results from the Ballistometer(®) and Cutometer(®).

BACKGROUND: Long-term exposure to sunlight changes skin features like amount of facial wrinkling and skin elasticity, which is useful in estimating skin health and age-related changes. Skin elasticity is evaluated by quantitative methods such as the noninvasive suction device Cutometer(®) , which is widely used to evaluate regional body-elasticity differences and correlate these findings with the results of other instrumental data. Few field studies have been done with the Ballistometer(®) device, another noninvasive method for measuring skin elasticity. METHOD: In this study, we measured the skin elasticity of each subject's forehead, cheek, and volar forearm using two devices with different means of obtaining quantitative measurements - Ballistometer(®) (Diastron Ltd.) and Cutometer(®) (CK electronics). RESULTS: The results from testing with the Ballistometer(®) and Cutometer(®) devices showed that the degree of skin elasticity of the volar forearm is greater than those found on the cheek and forehead. The parameters measured by the Ballistometer(®) showed high correlation patterns. On the cheek skin, the correlation coefficient between Ballisto-parameters and R parameters (R0, R3, R8) was higher than other skin sites. CONCLUSION: Taken together, R parameters measured by the Cutometer(®) device have been widely distributed in the evaluation of skin elasticity in research and cosmetics. Although the methodologies are different, the Ballistometer(®) device is also a useful tool to evaluate skin elasticity.

Establishment of a reliable and reproducible murine osteoarthritis model.

OBJECTIVE: Many osteoarthritis (OA) models have been developed in mice to understand OA progression and evaluate new OA therapies. However, the individual variation of the joint lesions remains a critical problem in most of the current OA models. We established an OA model in C57BL/6 mice that is more reproducible and amenable to therapeutic intervention by controlling their movement. DESIGN: OA was induced in 9-week-old C57BL/6 mice by destabilizing the medial meniscus. The mice were then raised in the standard cage for free movement or in a confined cage customized to restrict movement. Mice in the confined cage were subjected to no exercise or exercise of 400, 800, and 1200 m/day. RESULTS: OA lesions of mice in the confined cage were more severe in the exercise group and showed much less variation. However, the patterns of OA lesions over time were quite different depending on the amount of daily exercise; the patterns increased linearly until 8 weeks in 400 m/day exercise group, but showed plateauing after 4 weeks in 800 m/day and 1200 m/day groups. The validity of our novel OA model with movement control was proven by successfully discriminating the therapeutic effect of hyaluronic acid (HA) in histological scores, while the OA model using standard caging showed a statistically insignificant difference. CONCLUSION: The mouse OA model using the confine cage and enforced periodic exercise of mice is more reproducible and reliable than standard caging methods.

Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer.

BACKGROUND: We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC). METHODS: Sunitinib (37.5 or 25 mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity. RESULTS: Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80 mg/m(2), and capecitabine 1,000 mg/m(2); sunitinib 37.5 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 800 mg/m(2); and sunitinib 25 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 1,000 mg/m(2). DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug-drug interactions were apparent. At the MTDs, median progression-free survival was 6.4 months and 5.5-8.0 months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7% and 43.5-45.5% for sunitinib/XP and sunitinib/XELOX, respectively. CONCLUSIONS: At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.

Expression analysis of rice VQ genes in response to biotic and abiotic stresses.

WRKY transcription factors are encoded by a large gene superfamily with a broad range of roles in plants. Proteins containing a short VQ (FxxxVQxLTG) motif have been recently shown to interact with WRKY transcription factors, implying that AtVQ proteins are important in the plant defense responses in Arabidopsis, either as positive or negative cofactors of WRKY transcription factors. Thirty-nine Oryza sativa genes containing the VQ motif (OsVQs) were identified and the genome structures of OsVQ proteins were characterized through genome-wide analysis in rice. Also, phylogenetic tree analysis was performed with the VQ domain of Arabidopsis and rice. The expression patterns of these OsVQ genes in plants under several stress treatments were assessed, specifically, following infection with the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), treatment with abscisic acid (ABA), or exposure to drought. The cellular localization of a few OsVQ proteins was examined using rice protoplast system. Based on our results, we suggest that OsVQ proteins function as important co-regulators during the plant defense response to biotic and abiotic stresses.

Association of a single nucleotide polymorphism in the akirin 2 gene with economically important traits in Korean native cattle.

The akirin 2 gene, located on chromosome 9 in cattle, was previously reported to be associated with nuclear factor-kappa B (NF-κB), involved in immune reactions and marbling of meat. To determine whether a single nucleotide polymorphism (SNP) in akirin 2 is associated with economically important traits of Korean native cattle, the c.*188G>A SNP DNA marker in the 3'-UTR region of akirin 2 was analyzed for its association with carcass weight, longissimus muscle area and marbling. The c.*188G>A SNP was genotyped by polymerase chain reaction restriction fragment length polymorphism, and the frequency of the AA, AG, and GG genotypes were 6.82%, 71.29% and 21.88% respectively. This SNP was significantly associated with longissimus muscle area (Bonferroni corrected P < 0.05), and marbling score (Bonferroni corrected P < 0.01). These results suggest that the c.*188G>A SNP of akirin 2 might be useful as a DNA marker for longissimus muscle area and marbling scores in Korean native cattle.

Inhibitory effect of tianeptine on catagen induction in alopecia areata-like lesions induced by ultrasonic wave stress in mice.

BACKGROUND: Alopecia areata (AA) is characterized by rapid and complete hair loss in one or multiple areas of the scalp. Stress is an important triggering factor in AA. AIM: To identify the inhibitory effect of tianeptine on catagen induction in C57BL/6 mice with AA-like lesions induced by ultrasonic wave stress (UWS). METHODS: The mice were divided into four groups. Group 1 received oral tianeptine before and after UWS; group 2 received oral tianeptine only after UWS; group 3 was given UWS treatment only; and group 4 (negative control group) was not given any treatment. Phototrichigraphy and dermatoscopy were used for assessment. Histological analysis was performed using haematoxylin and eosin, toluidine blue, Masson trichrome and Verhoeff-van Gieson stains. Immunohistochemical analysis was also performed. The level of apoptosis and expression of neuropeptides in the skin were assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling and immunofluorescence assays. RESULTS: Mice in group 1 had an increased rate of hair growth and greater hair-shaft thickness compared with mice in groups 2 and 3. In addition, mice in group 1 had a higher number of anagen hair follicles, increased synthesis of collagen and elastic fibres, decreased mast-cell degranulation, reduction in cell apoptosis in hair follicles, and recovery of vitamin D receptor expression. Expression of neuropeptides (substance P, calcitonin gene-related peptide) was not altered. CONCLUSIONS: Tianeptine might play a role in suppressing catagen induction in a stress-induced AA mouse model.

A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

BACKGROUND: PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer. PATIENTS AND METHODS: Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m(2), irinotecan 300 mg/m(2) or docetaxel (Taxotere) 75 mg/m(2) every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error ß = 0.10, null hypothesis of ORR was 5%). RESULTS: Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%). CONCLUSION: The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting.

Effect of complementary and alternative medicine on the survival and health-related quality of life among terminally ill cancer patients: a prospective cohort study.

BACKGROUND: We evaluated whether complementary and alternative medicine (CAM) use influenced outcomes [survival and health-related quality of life (HRQOL)] of cancer patients whose condition had just been judged terminal. PATIENTS AND METHODS: From July 2005 to October 2006, we conducted a prospective cohort study of 481 terminally ill cancer patients at 11 university hospitals and the National Cancer Center in Korea. We assessed how the use of CAM affected HRQOL and survival. RESULTS: In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased cases. On multivariate analyses, CAM users did not have better survival compared with nonusers [adjusted hazard ratio (aHR), 0.91; 95% confidence interval (CI) 0.74-1.10]. Among mind-body interventions, prayer showed significantly worse survival (aHR, 1.56; 95% CI, 1.00-2.43). Clinically, CAM users reported significantly worse cognitive functioning (-11.6 versus -1.3; P < 0.05) and fatigue (9.9 versus -1.0; P < 0.05) than nonusers. Compared with nonusers in subgroup analysis, users of alternative medical treatments, prayer, vitamin supplements, mushrooms, or rice and cereal reported clinically significant worse changes in some HRQOL subscales. CONCLUSION: While CAM did not provide any definite survival benefit, CAM users reported clinically significant worse HRQOLs.